Eli Lilly and AstraZeneca announced that they are stopping two global Phase 3 trials of lanabecestat, an amyloid beta-targeting treatment candidate for Alzheimer’s, because of an apparent lack of benefit. Safety was not of concern in either trial.
The decision follows recommendations by an independent data monitoring committee, which concluded that both trials — the AMARANTH Phase 2/3 study (NCT02245737) in early Alzheimer’s patients and the DAYBREAK-ALZ Phase 3 trial (NCT02783573) in those with mild Alzheimer’s-associated dementia — were unlikely to meet their primary endpoints or goals.
Both studies were assessing improvements in cognitive performance using a 13-item test called the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, or ADAS-Cog13.
Lanabecestat is a small-molecule, oral inhibitor of the beta secretase cleaving enzyme (BACE), which is a key enzyme in the formation of amyloid beta — the main component of senile plaques.
“The complexity of Alzheimer’s disease poses one of the most difficult medical challenges of our time, and we are deeply disappointed for the millions suffering from this devastating disease,” Daniel Skovronsky, MD, PhD, president of Lilly Research Labs, said in a press release.
“We are grateful for the contributions of the study participants and their families and encourage them to consider other Alzheimer’s disease clinical trials,” Skovronsky added. He also reaffirmed the company’s commitment to finding treatments for Alzheimer’s patients.
Noting that safety concerns were not part of the decision to halt the trials, boht companies noted that the Lilly and AstraZeneca BACE Alliance for lanabecestat is still in place. Eli Lilly and AstraZeneca will work with study sites in discontinuing the trials.
“We are saddened by this outcome as our researchers are working tirelessly to find a solution for the many people who are impacted by this devastating disease,” Menelas Pangalos, PhD, Executive Vice President, IMED Biotech Unit at AstraZeneca, commented. “We are committed to ensuring our findings can be used to inform further research in the Alzheimer’s community.”
AMARANTH was assessing the efficacy and safety of lanabecestat over 104 weeks of treatment in people with early Alzheimer’s. Patients were randomly assigned to either lanabecestat – 20mg or 50mg – or placebo in a once-daily oral dose. An associated extension trial – where patients who completed the AMARANTH study were invited to enroll and receive active treatment – will also be stopped.
DAYBREAK-ALZ was evaluating the efficacy of 20mg or 50mg doses of lanabecestat, or placebo, once daily for up to 156 weeks in patients with mild Alzheimer’s.
That company announced in May that both the Phase 2b/3 EARLY study (NCT02569398) in late-onset preclinical (asymptomatic) Alzheimer’s and a Phase 2 safety trial were stopped due to toxicity concerns after serious elevations in liver enzymes were reported in some study participants.